AJP - Cell Physiology, Vol 260, Issue 2 C234-C241, Copyright © 1991 by American Physiological Society
Stimulation by cGMP of apical Na channels and cation channels in toad urinary bladder
S. Das, M. Garepapaghi and L. G. Palmer
Department of Physiology, Cornell University Medical College, New York, New York 10021.
The effects of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) on
apical membrane cation conductances in the toad urinary bladder were
investigated. 8-BrcGMP (1 mM) added to the serosal solution increased the
amiloride-sensitive short-circuit current (INa) after a delay of 5 min to a
steady-state value 1.8 times that of controls achieved after 30 min.
Similar effects were seen when the bladders were bathed on the serosal side
with a normal NaCl Ringer solution and with a high-K sucrose solution to
depolarize the basolateral membrane. Under the latter conditions, the
amiloride-sensitive transepithelial conductance increased in parallel with
the short-circuit current, indicating stimulation of apical membrane Na
channels. The threshold concentration for observing the stimulation of INa
was 100 microM, 10-100 times larger than the concentration of
8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) required to elicit
an increase in INa. Currents through an outwardly rectifying Ca-sensitive
cation conductance (Iout) were also increased by 1.8-fold relative to
controls. This stimulatory effect occurred after a delay of 15 min and
reached maximal levels 90-120 min after addition of the nucleotide. The
effects of cGMP on INa were not additive with those of 8-BrcAMP or with
antidiuretic hormone, an agent known to act by increasing cAMP within the
cell. Addition of 1 mM 3-isobutyl-1-methylxanthine to the serosal side of
the bladders stimulated INa by 1.3-fold and Iout by 2.4-fold. In both
cases, subsequent addition of cGMP produced no further activation of either
conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
